5-Prime | Ribozymes
1. What's a ribozyme? It is a catalytic RNA molecule. That discovery won the 1989 Nobel Prize in Chemistry for Tom Cech and Sidney Altman. Eight classes of ribozymes have now been identified, including seven that modify the nucleic acid backbone: hammerhead, hairpin, HDV (hepatitis delta virus), ribonuclease P, group I intron, group II intron, and VS ribozyme. The eighth type, the ribosome's peptidyl transferase center, builds peptide bonds.
2. What's all the fuss about? Two things, really. First, some researchers believe that the predecessor of the current DNA-RNA-protein world was an RNA world, in which RNA encoded both information, like DNA does, and function, as protein does. Ribozyme researchers hope to gain a glimpse of what that RNA world was like by studying ribozymes. Second, a number of researchers have had success using "in vitro evolution" to derive novel ribozyme activities.
3. Novel ribozyme activities? How do they do that? Through a process of directed evolution. Scientists begin with a pool of around 1015 random RNA molecules. They then drain that pool using multiple rounds of selection, reverse transcription, PCR amplification, and transcription. The researcher may even tailor the selection procedure to make the final molecule subject to allosteric regulation.
4. What's allosteric regulation? That's when a ribozyme's activity is dependent, either positively or negatively, on a small molecule, metal ion, or protein--whatever the scientist chooses to regulate the enzyme. RNA molecules that bind analytes are called aptamers. An allosteric ribozyme, basically a fused aptamer and ribozyme, is sometimes called an aptazyme.
5. Is there any value to ribozymes outside of academic curiosity? Yes! Several companies, including Archemix, Ribozyme Pharmaceuticals, and Immusol, are developing diagnostic and therapeutic agents based on ribozymes and aptazymes.
--Jeffrey M. Perkel